MN1 overexpression is an important step in the development of inv(16) AML

• Published in: Leukemia Vol. 21; no. 8; pp. 1679 - 1690
• Main Authors: CARELLA, C, BONTEN, J, GROSVELD, G. C, SIRMA, S, KRANENBURG, T. A, TERRANOVA, S, KLEIN-GELTINK, R, SHURTLEFF, S, DOWNING, J. R, ZWARTHOFF, E. C, LIU, P. P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-08-2007; Nature Publishing Group
• Subjects: Abnormalities; Acute Disease; Acute myeloid leukemia; Animals; Biological and medical sciences; Bone marrow; Bone Marrow Transplantation; Care and treatment; Cell culture; Cells, Cultured; Chromosome Inversion; Chromosome translocations; Chromosomes, Human, Pair 16 - genetics; Development and progression; Female; Flow Cytometry; Gene Expression Regulation, Neoplastic - physiology; Genes; Genetic aspects; Hematologic and hematopoietic diseases; Humans; Leukemia; Leukemia, Myeloid - etiology; Leukemia, Myeloid - metabolism; Leukemia, Myeloid - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical prognosis; Medical sciences; Meningioma; Mice; Mice, Transgenic; Mimicry; Myelocytic leukemia; Myeloproliferative diseases; Myeloproliferative Disorders - etiology; Myeloproliferative Disorders - metabolism; Myeloproliferative Disorders - pathology; Nonlymphoid leukemia; Oncogene Proteins - genetics; Oncogene Proteins, Fusion - genetics; Oncogene Proteins, Fusion - metabolism; Patients; Physiological aspects; Proteins; Survival Rate; Transcription; Translocation; Translocation, Genetic - genetics; Transplants; Transplants & implants; Tumor suppressor genes; United States > US; AML; inv; MN1; Hematology; Gene overexpression; Malignant hemopathy; CBFβ-SMMHC; Acute myelocytic leukemia
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2404778

The gene encoding the transcriptional co-activator MN1 is the target of the reciprocal chromosome translocation (12;22)(p13;q12) in some patients with acute myeloid leukemia (AML). In addition, expression array analysis showed that MN1 was overexpressed in AML specified by inv(16), in some AML overexpressing ecotropic viral integration 1 site (EVI1) and in some AML without karyotypic abnormalities. Here we describe that mice receiving transplants of bone marrow (BM) overexpressing MN1 rapidly developed myeloproliferative disease (MPD). This BM also generated myeloid cell lines in culture. By mimicking the situation in human inv(16) AML, forced coexpression of MN1 and Cbfbeta-SMMHC rapidly caused AML in mice. These findings identify MN1 as a highly effective hematopoietic oncogene and suggest that MN1 overexpression is an important cooperative event in human inv(16) AML.